FerroDRP1 · Deciphering the role of DRP1 in the spatio-temporal regulation of lipid peroxidation during ferroptosis

Линиите свързват координатора с партньорите.

Накратко на български

Цел на проекта

Ferroptosis is an iron-dependent, regulated form of cell death marked by lipid peroxidation, with emerging relevance across several diseases like neurodegeneration and therapy-resistant cancer. While lipid peroxidation is central to ferroptosis, the mechanisms underlying its intracellular spread remain poorly understood. Recent findings identify the mitochondrial fission protein DRP1 as a key driver of ferroptosis, linking its established role in mitochondrial dynamics and fragmentation to the regulation and redistribution of peroxidized lipids. However, how DRP1 mechanistically coordinates the spatial and temporal propagation of lipid peroxidation across organelles under ferroptotic conditions remains unresolved.This project will systematically dissect DRP1's functions in ferroptosis through three integrated objectives: (1) investigating how DRP1 interfaces with key antioxidant systems, including the GPX4-glutathione and FSP1-CoQ10-NAD(P)H pathways, to impact ferroptotic sensitivity and cellular redox balance; (2) elucidating the effects of DRP1-driven mitochondrial remodelling and metabolic reprogramming on lipid peroxidation dynamics and ferroptosis susceptibility and (3) determining whether DRP1 modulates endoplasmic reticulum–mitochondria contact sites (ERMCS) to facilitate lipid peroxidation spread;. Using DRP1 knockout and wild-type cell models, I will combine super-resolution imaging, biochemical fractionation, genetic editing, and metabolic flux analysis to map these processes comprehensively. By clarifying how DRP1 orchestrates mitochondrial dynamics, organelle crosstalk, and lipid homeostasis during ferroptosis, this work aims to uncover novel molecular intervention points for diseases where ferroptosis is either pathogenic or therapeutically exploited.

Оригинален текст от CORDIS (на английски).

Участници

• MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENКоординаторГермания

Връзки

• Виж в CORDIS
• DOI: 10.3030/101278714